以视力损失及OCT改变为首发症状的白血病

目的:报告2例以视力下降为首发症状的白血病患者,采用光学相干断层扫描(OCT)识别和定位视网膜病变。方法:回顾性干涉个案报告。结果:伴随视力下降,确诊急性淋巴细胞白血病和慢性淋巴细胞白血病患者各1例。OCT发现1例为黄斑部浆液性脱离。另1例为视网膜低荧光浸润,OCT表现为高反射性损伤。在随访时间内,肿瘤完全缓解后视网膜改变消失,视力明显恢复。结论:OCT是一种检测、定位和跟踪的眼部肿瘤有价值的,非侵入性的诊断工具。     

HTLV-1 Tax 基因真核表达载体的构建及对 RPE 细胞的影响

目的构建人T淋巴细胞白血病病毒-1(human T-cell leukemia virus type1,HTLV-1)Tax基因真核表达载体,在人视网膜色素上皮(retinal pigment epithelium,RPE)细胞表达Tax蛋白,观察其对细胞的影响。方法应用基因重组技术构建重组载体PIRES2-EGFP-Tax(PT),鉴定后将重组载体转染入RPE细胞,应用RT-PCR、Western-blot和免疫荧光法检测细胞内Tax基因和蛋白的表达;通过MTT和流式细胞仪检测质粒(空白载体、PT和Green-Tax)转染RPE细胞24h和48h后对RPE细胞生长活力及细胞周期的影响。结果经双酶切鉴定和测序分析证实成功地构建了HTLV-1Tax真核表达载体;通过RT-PCR、Western-blot和免疫荧光法检测到转染Tax重组载体的RPE细胞中有Tax基因和蛋白的表达。质粒转染RPE细胞后,细胞生长活力受到抑制,G1期减少而S期增加。但转染Tax质粒和空白载体,对RPE细胞的生长活力和细胞周期产生相似影响。结论成功构建了HTLV-1Tax基因真核表达载体,并在RPE细胞中表达Tax蛋白;Tax质粒对RPE细胞的影响不排除是转染试剂所致。     

巨细胞病毒性视网膜炎

探讨免疫功能低下患者中巨细胞病毒性视网膜炎的临床表现、诊断及治疗。方法 :观察分析 6 1例巨细胞病毒 (cytomeglovirus ,CMV)性视网膜炎患者 10 4只眼 ,对其眼底、视力、T辅助细胞的细胞受体4(CD4 )计数及预后进行观察随访 2周～ 18个月。结果 :6 1例CMV视网膜炎中 ,5 6例为获得性免疫缺陷综合征 (acquiredimmunodeficiencysyndrome ,AIDS)患者 ,1例为应用免疫抑制剂的肾移植患者 ,1例为接受化疗的急性淋巴细胞性白血病患者 ,3例为白血病同时合并AIDS患者。 10 4眼 6 1例患者中 ,眼底病灶表现为颗粒型者 5 8眼 ,其中 46眼位于周边部 ;爆发型者 2 8眼 ,均位于后极部 ,视网膜坏死灶致密伴斑片状出血和血管炎 ;颗粒型与爆发型病灶混合存在者 18眼 ;其中 7眼合并有视神经乳头炎 ;患者就诊时视力为眼前指数至 0 5 ,病变广泛者及病变位于后极部者视力下降尤为严重。 30例患者CD4 细胞计数为 0～ 30个 /μl,平均 15± 9个 /μl。接受更喜洛韦治疗组患者视力多数提高 ,CD4 T细胞计数明显升高 ,未治疗组患者 93 %病变呈进行性发展 ,视力显著下降。结论 :CMV视网膜炎是免疫功能严重低下患者 ,尤其AIDS病的主要眼部并发症 ,临床上以坏死性视网膜炎伴出血及血管炎为特征 ,治疗目前主要用更昔洛韦。     

小儿急性白血病眼部并发症25例报告

急性白血病是儿童最常见恶性肿瘤，眼部是常被累及的组织器官之一，有时以眼部病变为首发表现。本文报告２５例眼部受累的急性白血病患儿，以高危急淋和急单发病最多，出现眼部合并症时间多在急白发病后１～１年半，主要症状有眼部疼痛、结膜充血、流泪、视力减退，白血病...     

获得性免疫缺陷综合征并发视网膜病变的眼部表现

眼部表现往往是获得性免疫缺陷综合征(AIDS)患者全身播散性感染的首要表现,大约45%～75%的AIDS患者眼部会受到侵犯[1].AIDS的眼部表现包括人类免疫缺陷病毒(HIV)视网膜微血管病变,病毒、细菌、真菌等各种机会性感染及眼内淋巴瘤等[2-4].其中以HIV视网膜微血管病变和巨细胞病毒性视网膜炎(CMVR)最为常见[2,5].近年来,AIDS患者逐渐增多,正确认识其眼部表现对早期珍治该病有着重要的临床意义.为此,我们观察了一组AIDS患者的典型眼部表现及治疗情况,现将结果报道如下.     

白血病合并原发性眼眶外周T淋巴细胞瘤一例

一例47岁男性患者,以眼部为原发表现,左眼鼻上方球壁外结膜组织浸润性生长,既往白血病病史,初诊MRI、PET-CT及病理活检均提示炎性病变可能,但经抗炎治疗无效,最终行手术摘除病灶后病理诊断为外周T细胞淋巴瘤非特指型,经CHOP方案化疗后病情缓解。（眼科,2022,31:403-404）     

人类免疫缺陷病毒感染及获得性免疫缺陷综合征患者眼部病变的诊断与治疗

目的 探讨人类免疫缺陷病毒(HIV)感染及获得性免疫缺陷综合征(AIDS)患者的眼部病变特点、临床症状及治疗原则.方法 回顾性系列病例研究.回顾性分析110例(220只眼)HIV感染和AIDS患者的临床资料,包括患者视力、眼前节、眼底检查和荧光素眼底血管造影及外周血CD_4~+T淋巴细胞检测结果,其中2例(4只眼)AIDS合并巨细胞病毒(CMV)性视网膜炎患者施行了更昔洛韦玻璃体腔注药治疗.患者年龄、HIV感染时间与HIV视网膜病变及CMV性视网膜炎的相关性采用Pearson相关分析法,性别与HIV视网膜病变及CMV性视网膜炎的相关性采用Pearson ChiSquare分析法,正常眼底组、HIV视网膜病变组、CMV性视网膜炎组间CD_4~+T淋巴细胞计数比较采用多个独立样本的秩和检验.结果 患者初诊视力为无光感者5只眼,光感至0.04者10只眼,0.05～0.2者14只眼,0.3～0.7者62只眼,0.8及以上者129只眼.110例(220只眼)HIV感染和AIDS患者中,有25只眼角膜后有灰白色细小或色素性沉着物.22只眼房水闪光(+)或(++).4只眼虹膜后粘连.28只眼晶状体混浊.34只眼确诊为HIV视网膜病变,眼底表现为棉絮斑、视网膜出血及微血管瘤.32只眼确诊为AIDS合并CMV性视网膜炎,26只眼的眼底表现为沿血管分布的浓厚黄白色病损区,其上片状出血,边缘有不规则黄白色颗粒.3只眼为眼底病变晚期,表现为视网膜萎缩、视网膜血管硬化和狭窄、视神经萎缩.3只眼合并视网膜脱离.正常眼底的HIV感染者及AIDS患者CD_4~+T淋巴细胞计数中位数为100.0个/mm~3,HIV视网膜病变患者CD_4~+T淋巴细胞计数中位数为41.0个/mm~3,CMV性视网膜炎患者CD_4~+T淋巴细胞计数中位数为18.0个/mm~3.CD_4~+T淋巴细胞计数比较,正常眼底组与HIV视网膜病变组相比,差异有统计学意义(x~2=4.848,P=0.028);正常眼底组与CMV性视网膜炎组相比,差异有统计学意义(x~2=15.696,P=0.000);HIV视网膜病变组与CMV性视网膜炎组相比,差异有统计学意义(x~2=4.860,P=0.027).2例(4只眼)CMV性视网膜炎患者行更昔洛韦(400 μg)玻璃体腔注药后,视力提高,眼底病变明显消退.结论 视网膜微血管病变是HIV感染及AIDS常见的眼部并发症,CMV性视网膜炎是AIDS晚期最严重的眼部并发症.高效抗逆转录病毒治疗可重建患者的免疫功能,更昔洛韦玻璃体腔注药可有效治疗CMV性视网膜炎并挽救患者视力.     

人类免疫缺陷病毒感染合并获得性免疫缺陷综合征眼部病变的眼底特征

目的 观察人类免疫缺陷病毒感染合并获得性免疫缺陷综合征(HIV/AIDS)的眼部病变眼底特征.方法 1041例HIV/AIDS患者纳入研究.其中,男性882例,占88.70％;女性159例,占11.30％;年龄12～73岁,平均年龄41岁.发现HIV感染时间为1个月～10年,平均HIV感染时间为12个月.传播方式为性传播475例,占45.63％;针头注射传播508例,占48.80％;输血传播44例,占4.25％;母婴传播14例,占1.34％.所有患者均进行视力、裂隙灯显微镜及眼底检查;发现眼底异常改变时行眼压、眼底照相及荧光素眼底血管造影(FFA)检查.观察不同眼部病变的眼底特征.结果 1041例HIV/AIDS患者中,发现眼部病变247例,占23.73％.其中,HIV视网膜微血管病变是最为常见的眼部病变,共132例,占眼部病变患者的53.44％;其次为巨细胞病毒性视网膜炎(CMVR),共70例,占眼部病变患者的28.34％.眼底检查发现,HIV视网膜微血管病变眼底表现为视网膜微动脉瘤,沿血管走行的灶状出血、棉绒斑;CMVR眼底表现为不规则干燥外观,颗粒状边沿,有的累积视神经.FFA检查发现,HIV视网膜微血管病变表现为出血斑呈遮蔽荧光,出血中心轻度强荧光,无荧光渗漏;CMVR表现为大片出血遮蔽荧光,血管荧光渗漏和(或)脉络膜透见荧光,视盘及病变区域荧光着染.结论 HIV/AIDS可发生多种眼部病变,以HIV视网膜微血管病变和CMVR最为常见.HIV视网膜微血管病变主要表现为灶状出血和(或)棉绒斑,CMVR主要表现为不规则干燥外观病变,有时合并大片出血.     

首诊眼科白血病1例

我院于2004年11月收治1例首诊眼部病变的白血病患者，现报告如下。     

人类免疫缺陷病毒感染的眼部并发症

近年来,随着高效抗逆转录病毒治疗法(HAART)的广泛应用,人类免疫缺陷病毒(HIV)和获得性免疫缺陷综合征(AIDS)相关眼部并发症的发病率显著降低。而HIV感染者和AIDS患者数量逐年增加,且生存率提高、生存时间延长,这导致发生眼部并发症的患者绝对数增多。其相关眼部并发症临床表现多变,几乎影响所有眼部结构。目前我国对HIV感染者和AIDS患者的眼部病变缺乏大样本和长期的系统观察,且临床诊疗中有误诊和漏诊的情况发生,这不但延误治疗,而且极易引起医源性传播,故医务工作者应加强对HIV/AIDS的了解。本文对HIV/AIDS患者常见眼部非感染性、机会性感染并发症和免疫重建炎症反应综合征(IRIS)进行综述,探讨HIV/AIDS眼部并发症的表现和研究进展。     

Ocular manifestations of human T-cell lymphotropic virus type 1 infection

PURPOSE OF REVIEW: Human T-cell lymphotropic virus type 1 (HTLV-1) infection is endemic in Japan, the Caribbean islands, and parts of Central Africa and South America. Known ophthalmic manifestations of HTLV-1 include malignant infiltrates in patients with adult T-cell leukemia/lymphoma, retinal degeneration, neuroophthalmic disorders, and keratoconjunctivitis sicca in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis, and HTLV-1-associated uveitis. This report reviews the recent developments and ocular findings reported in patients with HTLV-1-related diseases. RECENT FINDINGS: Most of the knowledge of the ocular manifestations of HTLV-1 comes from southwestern Japan, which has the highest incidence of infection worldwide. During the past few years, however, ocular disease associated with HTLV-1 has been described in patients from other endemic areas genetically distinct and geographically distant from Japan. The most interesting of these was the recognition of corneal pathology in Brazilian and Caribbean patients with HTLV-1 that have not been described in Japanese patients. Other developments include the use of molecular techniques in the diagnostic evaluation of ocular tissues from HTLV-1 patients, and clinical studies demonstrating choroidal involvement by indocyanine green angiography in patients with HTLV-1-associated uveitis, and suggesting that retinal vasculitis unresponsive to corticosteroid therapy maybe a poor prognostic sign. SUMMARY: The spectrum of ocular disease related to HTLV-1 continues to expand. Routine evaluation of HTLV-1-infected patients is important because immune-mediated or neoplastic ocular involvement may occur during the disease course. Genetic and environmental factors may play a role in the ocular manifestations of HTLV-1 in different populations.     

Human T-cell lymphotropic virus type-1 associated t-cell leukemia/lymphoma masquerading as necrotizing retinal vasculitis

OBJECTIVE: To report a case of adult T-cell leukemia/lymphoma (ATL) presenting as a bilateral retinal vasculitis and diagnosed by molecular detection of a rearrangement in the T-cell receptor (TCR) and the presence of the human T-cell lymphotropic virus type 1 (HTLV-1) pol gene in the malignant lymphoid cells. DESIGN: Case report. METHODS: Routine histologic and immunohistochemical analyses were performed on the retinal biopsy specimen before referral to the National Eye Institute. Lymphoid cells associated with granulomatous inflammation infiltrating the retina and surrounding retinal blood vessels were microdissected from the paraffin sections of the retinal biopsy specimen. The polymerase chain reaction (PCR) was performed using primers for the TCR gene and HTLV-1 pol and gag genes. RESULTS: Microscopic examination showed a necrotizing granulomatous retinal vasculitis with a predominant T-cell infiltrate detected by immunohistochemistry. Molecular analysis demonstrated a clonal rearrangement of the TCR and the presence of the HTLV-1 pol gene in the microdissected lymphoid cells diagnostic of ATL. CONCLUSIONS: Necrotizing retinitis and retinal vasculitis are rare manifestations of ATL. Human T-cell lymphotropic virus type 1 infection should be considered in the differential diagnosis of patients from endemic areas who have retinal vasculitis at presentation. This case further demonstrates the usefulness of microdissection and PCR for the diagnosis of ocular disease, including HTLV-1 infection.     

Retinal Vasculitis Caused by Adult T-cell Leukemia/Lymphoma

Background To report a case of lymphomatous infiltration and bilateral retinal vasculitis observed among 83 cases of adult T-cell leukemia (ATL) treated in the University Hospital Center in Fort-de-France (Martinique, French West Indies) between 1984 and 2003.Case A complete clinical ophthalmologic examination was performed in this patient along with fluorescein angiography.Observations After being checked for diffuse adenopathies, myodesopsias, and phosphenes, the 35-year-old patient was diagnosed with ATL. The ocular impairment, present since the onset of ATL as peripheral subretinal infiltrates, spread progressively and afferently to the rest of the retina in the form of an essentially venous vasculitis. Impairment of the vitreous was noted only in the end stages of disease progression. As ocular lesions progressed, the general state of the patient degraded at the same time despite chemotherapeutic measures.Conclusion Among the more than 300 seropositive for human T-cell lymphotropic virus type 1 (HTLV-1) or patients with HTLV-1-associated myelopathy/tropical spastic paraparesis treated at our hospital in the last 20 years, and among the 83 cases of ATL, only this single case of retinal vasculitis associated with HTLV-1 was observed (1/83, 1.2%) in Martinique, confirming the geographic variability of the clinical phenotype of HTLV-1 infection. The incidence of retinal vasculitis in ATL patients may signify an even worse prognosis than initially indicated. Jpn J Ophthalmol 2005;49:41–45 © Japanese Ophthalmological Society 2005     

Ocular lesions in 200 patients infected by the human T-cell lymphotropic virus type 1 in martinique (French West Indies)

PURPOSE: To describe the ophthalmologic features observed in patients infected by the human T-cell lymphotropic virus, type 1 (HTLV-1) in Martinique (French West Indies). DESIGN: Prospective consecutive observational case series. METHODS: A complete ophthalmic examination was performed. PATIENTS: Of 200 patients infected by HTLV-1, 77 (38.5%) were seropositive and 123 (61.5%) had HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). RESULTS: Uveitis was found in 29 cases (14.5%). Symptoms were mild and the uveitis had little effect on visual function. Ten cases of uveitis were discovered through a systematic examination and had no ocular symptoms. Most of the uveitis was anterior or intermediate. The lesions responded to corticosteroid therapy, but tended to recur. Keratoconjunctivitis sicca existed in 74 patients (37%), accompanied by lymphoplasmocytoid infiltration of the secondary salivary glands rated 3 or 4 on the Chisholm scale in nearly 50% of cases. Corneal alterations were observed in 20 cases (10%), and alterations in the retinal pigment epithelium in 3 cases. CONCLUSION: The three types of ocular affections seen most frequently were uveitis, keratoconjunctivitis sicca, and interstitial keratitis. In patients with HAM/TSP, uveitis was more frequent among younger patients, patients with earlier onset of HAM/TSP, and patients with severe motor disability. Because uveitis is related to a high intrathecal production of immunoglobulin, it could represent a marker for severity of HTLV-1 infection with respect to the course of HAM/TSP. The sicca syndrome related to HTLV-1 virus differs from primary or secondary Sj?gren syndrome, because it does not reveal any of the immunologic anomalies generally seen in this disease. Interstitial keratitis was more frequent among patients with HAM/TSP who had high proviral DNA levels.     

Human T-cell lymphotropic virus type 1-associated retinal vasculitis in children.

PURPOSE: To describe predominant retinal vasculitis in children carrying human T-cell lymphotropic virus type 1 (HTLV-1). METHODS: The authors examined clinical records of patients with HTLV-1-associated uveitis between 1987 and 2001 in Kagoshima University Hospital and reviewed cases of extensive, smoldering retinal vasculitis. RESULTS: Three previously healthy teenagers noted mild visual symptoms and presented with extensive sheathing of retinal vessels, complicated by mild anterior segment inflammation. The retinal vascular disease responded poorly to systemic corticosteroids, had a smoldering course with persistent sheathing of retinal vessels, and eventually resulted in diffuse chorioretinal degeneration. Results of laboratory studies were unremarkable except for the presence of serum antibodies to HTLV-1. One patient developed HTLV-1-associated myelopathy 11 years after the onset of ocular disease. CONCLUSIONS: The retinal vasculitis differed from the retinal vascular changes commonly seen in HTLV-1-associated uveitis. The authors suggest a clinical disease HTLV-1-associated retinal vasculitis that affects young HTLV-1 carriers, characterized by smoldering retinal vasculitis with ultimate retinal degeneration.     

Immunologic markers, uveitis, and keratoconjunctivitis sicca associated with human T-cell lymphotropic virus type 1

PURPOSE: To verify the occurrence of keratoconjunctivitis sicca (KCS) and human T-cell lymphotropic virus type 1 (HTLV-1) associated uveitis (HAU) and to evaluate the immunologic status related to HTLV-1. DESIGN: Cross-sectional study. METHODS: Ophthalmic examination (both eyes) and immunophenotyping of peripheral blood lymphocytes were performed in 207 infected asymptomatic blood donors (AS), 55 controls (NI), and 55 patients with HTLV-1 associated myelopathy (HAM/TSP). Examiner was masked to patient's serologic status. RESULTS: KCS was more frequent in HAM/TSP (30/55, 54.5%) than in NI and AS (07/55, 12.7% and 42/207, 20.3%, respectively). Presence of lacrimal hyposecretion in KCS individuals was higher in the HAM/TSP group (P < .001) as compared with NI and AS. HAU was found in 1/55 (1.82%) of HAM/TSP patients and 4/207 (1.93%) of HTLV-1 seropositive donors. Higher levels of activated CD4(+) and CD8(+) T cells were observed in HAM/TSP. Patients with HAU displayed higher percentage of both CD4(+) HLA-DR(+) and CD8(+)HLA-DR(+) when compared with NI and AS without HAU. CONCLUSIONS: Patients with HAM/TSP manifested more ophthalmologic symptoms than asymptomatic HTLV-1-infected individuals, with significantly higher KCS and immunologic alterations. Levels of activated CD8+ T cells could be used as a prognosis marker of inflammatory disease manifestation to follow-up AS individuals.     

Interleukin-2 Receptor Targeted Therapy of Ocular Disease of HTLV-1-associated Adult T-cell Leukemia

Purpose: To report two cases of patients with ocular manifestations of human T-cell lymphotropic virus type-1 (HTLV-1) associated adult T-cell leukemia/lymphoma (ATL) who were successfully treated with interleukin-2 receptor targeted therapies.

Method: Case series.

Results: Two patients with HTLV-1-associated ATL developed symptomatic scleritis. In the first case, conjunctival biopsy showed leukemic infiltration that was confirmed by T-cell receptor polymerase chain reaction (PCR) demonstrating a clonal rearrangement. As treatment for ATL, both cases received interleukin-2 receptor targeted therapy. In one patient, daclizumab, a monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor, was used. The second patient was treated with denileukin diftitox, an immunotoxin fusion protein that targets the IL-2 receptor. Improvement in scleritis was noted in both patients.

Conclusion: Scleritis in patients with underlying HTLV-1-associated ATL is responsive to IL-2 receptor targeted therapies.     

Hypergammaglobulinemia and corneal opacities in patients with human T-cell lymphotrophic virus type-1

PURPOSE: To investigate the relationship between serum immunoglobulin levels and corneal opacities in a cohort of patients with human T-cell lymphotrophic virus type-1 (HTLV-1). DESIGN: Retrospective case series. METHODS: Complete ophthalmologic examination was performed on 44 patients with HTLV-1 infection (25 patients with adult T-cell leukemia/lymphoma [ATL], 18 patients with HTLV-1 that was associated myelopathy/tropical spastic paraparesis [HAM/TSP], and one patient who was asymptomatic). Corneal opacities were described by shape, size, color, and location. Serum immunoglobulin (Ig) levels (IgG, IgM, and IgA) were measured by nephelometry. RESULTS: Corneal opacities were identified in 15 of 25 patients (60%) with ATL and five of 18 patients (28%) with HAM/TSP. The prevalence of corneal opacities was associated statistically with elevated IgG level (P = .023) in patients with ATL, but not in patients with HAM/TSP (P > .99). CONCLUSION: Although the mechanism remains unclear, hypergammaglobulinemia is associated with the development of the corneal opacities in patients of African descent with ATL.     

Protective immunity against ocular herpes infection and disease induced by highly immunogenic self-adjuvanting glycoprotein D lipopeptide vaccines

PURPOSE: An important phase in the development of an ocular herpes simplex virus type 1 (HSV-1) subunit vaccine is the identification of an efficient, safe, and adjuvant-free antigen delivery system capable of inducing and sustaining long-term memory T-cell protective immunity. This study was conducted to test the hypothesis that immunization with self-adjuvanting lipopeptide bearing HSV-1 glycoprotein D (gD) T-cell epitopes would elicit long-term HSV-specific T cells and decrease infection, disease, or both in a ocular herpes mouse model. METHODS: Five immunodominant CD4(+) T-cell peptide epitopes (gD(1-29), gD(49-82), gD(146-179), gD(228-257), and gD(332-358)), recently identified from HSV-1 gD, were covalently linked to a palmitic acid moiety (lipopeptides) and delivered subcutaneously in adjuvant-free saline. The primary and memory T cells induced by these molecularly defined lipopeptides and their protective efficacy were assessed, in terms of virus replication in the eye, ocular disease, and survival. RESULTS: Three gD lipopeptides, that drive dendritic cell maturation in vitro, induced long-term, virus-specific, IFN-gamma-producing CD4(+) Th(1) responses, associated with a reduction in ocular herpes infection and disease. Immunization with a cocktail of these three highly immunogenic Th(1) lipopeptides increased survival, lowered the peak of ocular virus titer, and cleared the ocular disease. CONCLUSIONS: Vaccination with a mixture self-adjuvanting lipopeptides containing novel HSV-1 immunodominant gD T-cell epitopes protected mice from ocular herpes infection and disease. The strength of protective immunity induced by these lipopeptides together with their safety provide a molecularly defined vaccine formulation that could combat ocular herpes infection and disease in humans.